Several ways are known for printing biomolecules onto a substrate. In one known method, a needle is dipped in a liquid containing biomolecules to hold the liquid. The needle is subsequently brought close to or in contact with the desired position of the substrate to transfer the liquid onto the substrate.
Another method uses a microstamp. US2008/0280785 describes a fluidic nano/micro array chip for stamping a plurality of nano/micro liquid droplets of a plurality of sample solutions on a biochip. The chip comprises a liquid containing layer filled with and transporting the sample solutions; a vertical transporting layer comprising a plurality of vertical channels connected to the liquid containing layer, wherein the vertical channels can transport the sample solutions; and a stamping head layer comprising a plurality of stamping heads respectively connected to the vertical channels. Each of the stamping heads includes a pipe.
This chip allows printing many samples simultaneously. There is a limit on how small the size of the pipes can be made, which determines the size of the spots which constitute the microarray. While the resulting microarray is satisfactory for some cases, the limited homogeneity and the relatively large size of the spots which constitute the microarray limit its applications.
U.S. Pat. No. 5,948,621 discloses a molecular stamp comprising: a solid substrate support; a polymeric gel covalently bound to said solid support so as to form an exposed patterned surface, said patterned surface including a raised region comprising said polymeric gel and at least one indentation within said raised region; said polymeric gel having absorbed therein a liquid vehicle, said liquid vehicle having a first biomolecules dissolved or colloidally suspended therein. In one of the embodiments, the stamp is an array of microcapillaries filled with a polymeric gel and connected to reservoirs holding a solution/suspension of a biomolecules of interest. The microcapillaries are made of glass. The polymeric gel may be a hydrogel formed by crosslinking 6-acryloyl-beta-O-methylgalactoside.
It is a drawback of the array of microcapillaries that microcapillaries lack mechanical robustness for repetitive printing. The tip of the microcapillaries having very thin walls come into contact with the substrate to be printed. Also, the hydrogel used in U.S. Pat. No. 5,948,621 swells excessively to allow diffusion of large biomolecules. However, this excessive swelling also leads to poor mechanical strength of the gel. With these hydrogels, it is difficult to control the shape of the spots and the hydrogel easily wears during printing which limits the lifetime of the stamp to a small number of printings.